The role of cholecystokinin and the cholinergic system in intravenous amino acid-induced gallbladder emptying.
BACKGROUND
Recent studies have demonstrated that separate intravenous infusion of amino acids (IVAA) at high doses induces gallbladder emptying. However, little is known about the mechanisms mediating IVAA-induced gallbladder contraction.


OBJECTIVE
To investigate whether the effect of IVAA on gallbladder motility is mediated by the cholinergic system and/or cholecystokinin (CCK), the major hormonal stimulus for gallbladder contraction. Six healthy male volunteers were studied in random order on five occasions using: (a) IVAA, (b) loxiglumide (CR 1505, a selective CCK-A receptor antagonist), (c) IVAA plus loxiglumide, (d) atropine and (e) IVAA plus atropine. Gallbladder volumes (ultrasonography) and plasma CCK levels (radioimmunoassay) were determined every 15 min for 60 min before and for 120 min during intravenous infusion of amino acids (Vamin 18EF; 250 mg protein/kg/h) and/or loxiglumide (10 mg/kg/h) and/or atropine (0.005 mg/kg/h).


RESULTS
IVAA significantly (P < 0.05) reduced gallbladder volume from 32 +/- 5 ml to 17 +/- 2 ml but induced only a small and transient increase in plasma CCK levels. Loxiglumide given alone significantly (P < 0.05) increased fasting gallbladder volume to 190% of the basal value. IVAA-induced gallbladder emptying was completely abolished by loxiglumide. Maximal gallbladder relaxation during IVAA plus loxiglumide was not significantly different compared to loxiglumide given alone. Concomitant administration of atropine also significantly (P < 0.05) inhibited IVAA-induced gallbladder emptying.


CONCLUSIONS
In healthy volunteers intravenous infusion of high doses of amino acids results in a significant gallbladder contraction, which is inhibited by CCK-A receptor blockade and by atropine.
Gielkens
H A
HA
Department of Gastroenterology-Hepatology, Leiden University Medical Center, The Netherlands.
de Boer
S Y
SY
Lam
W F
WF
Rovati
L C
LC
Lamers
C B
CB
Masclee
A A
AA
D000328:Adult; D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology*; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D002766:Cholecystokinin / Q000097:blood / Q000502:physiology*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D005704:Gallbladder / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D011377:Proglumide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014463:Ultrasonography
D000596:Amino Acids; D006727:Hormone Antagonists; D018727:Muscarinic Antagonists; C053737:loxiglumide; D001285:Atropine; D002766:Cholecystokinin; D011377:Proglumide